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Data from: Oncogenic receptor tyrosine kinase signaling is driven by the Golgi protein GOLPH3 and its interaction with MYO18A

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May 19, 2026 version files 45.79 GB

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Abstract

Receptor tyrosine kinase (RTK) signaling drives cancer and is a validated therapeutic target. Modulators of RTK signaling can reveal mechanisms of oncogenesis and offer new therapeutic targets. Golgi phosphoprotein 3 (GOLPH3) is a Golgi-localized oncoprotein, known to affect signaling downstream of mTOR. Several mechanistic hypotheses have been suggested. Here, systematic examination of RTK signaling indicates that GOLPH3 acts at the RTK itself, affecting all downstream signaling. We find that GOLPH3 modulates delivery of RTKs to the plasma membrane. This role is shared with its binding partner Myosin 18A (MYO18A) and depends on the interaction of GOLPH3 with MYO18A. The GOLPH3-MYO18A complex at the Golgi is required and rate-limiting for RTK signaling across cell-types and receptors. Our findings provide a cohesive understanding of the relationship between GOLPH3’s function at the Golgi and its role as a cancer driver, highlighting its potential as a therapeutic target in cancer.